Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model.
Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model.
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发表时间：
2000-04
影响因子：
4
通讯作者：
A. Muraglia;R. Cancedda;R. Quarto
中科院分区：
文献类型：
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作者：
A. Muraglia;R. Cancedda;R. Quarto
骨髓基质细胞可以产生多种间充质谱系。已经提出了一种共同的干/祖细胞——间充质干细胞的存在，但这种间充质多能祖细胞遵循哪个发育阶段尚不清楚。基于实验证据，提出了一种间充质干细胞分化模型，其中各个谱系直接从同一祖细胞分支。我们通过使用骨髓来源的基质成纤维细胞的克隆培养物验证了该模型。我们分析了 185 个非永生化人骨髓基质细胞克隆分化成三个主要谱系的能力：成骨、软骨和脂肪形成。除一个克隆外，所有克隆均分化为成骨谱系。大约三分之一的克隆分化为所分析的所有三个谱系。大多数克隆（60-80%）显示出骨软骨形成潜力。我们从未观察到分化潜力仅限于骨脂肪形成或软骨脂肪形成表型的克隆，也没有观察到纯软骨形成和脂肪形成克隆。评估许多克隆的分化潜力在其整个生命周期中维持多长时间。随着细胞倍增的增加，克隆逐渐丧失其脂肪形成和软骨形成分化潜力。我们的数据提出了一种可能的预定骨髓基质细胞分化模型，其中三能细胞可以被视为早期间充质祖细胞，其显示出谱系潜能的连续丧失，产生骨软骨祖细胞，而骨软骨祖细胞反过来又产生成骨前体细胞。
Bone marrow stromal cells can give rise to several mesenchymal lineages. The existence of a common stem/progenitor cell, the mesenchymal stem cell, has been proposed, but which developmental stages follow this mesenchymal multipotent progenitor is not known. Based on experimental evidence, a model of mesenchymal stem cell differentiation has been proposed in which individual lineages branch directly from the same progenitor. We have verified this model by using clonal cultures of bone marrow derived stromal fibroblasts. We have analyzed the ability of 185 non-immortalized human bone marrow stromal cell clones to differentiate into the three main lineages: osteo-, chondro- and adipogenic. All clones but one differentiated into the osteogenic lineage. About one third of the clones differentiated into all three lineages analyzed. Most clones (60-80%) displayed an osteo-chondrogenic potential. We have never observed clones with a differentiation potential limited to the osteo-adipo- or to the chondro-adipogenic phenotype, nor pure chondrogenic and adipogenic clones. How long the differentiation potential of a number of clones was maintained was assessed throughout their life span. Clones progressively lost their adipogenic and chondrogenic differentiation potential at increasing cell doublings. Our data suggest a possible model of predetermined bone marrow stromal cells differentiation where the tripotent cells can be considered as early mesenchymal progenitors that display a sequential loss of lineage potentials, generating osteochondrogenic progenitors which, in turn, give rise to osteogenic precursors.